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Towards efficient immunotherapy for bacterial infection

生物 抗生素耐药性 重症监护医学 抗生素 疾病 抗生素治疗 传染病(医学专业) 抗菌剂 免疫疗法 免疫系统 微生物学 免疫学 医学 内科学
作者
Timothy R. McCulloch,Timothy J. Wells,Fernando Souza‐Fonseca‐Guimaraes
出处
期刊:Trends in Microbiology [Elsevier]
卷期号:30 (2): 158-169 被引量:55
标识
DOI:10.1016/j.tim.2021.05.005
摘要

Immunotherapy has revolutionized the treatment of cancer through the reversal of immunosuppression. Development of antibiotic resistance is a concerning trend that is reducing treatment options for bacterial infection. Cancer and bacterial infections share many hallmarks of suppression, suggesting that immunotherapy could also be a revolutionary tool for clinics to treat bacterial infections, including troublesome persistent and antibiotic-resistant infections such as tuberculosis. Preclinical data are rapidly emerging, showing that immune checkpoint inhibition, modulation of cytokines, and cellular therapies hold great promise for treating various bacterial infections. Clinical trials are urgently needed to determine the effectiveness and safety of utilizing immunotherapy in the face of the looming antibiotic-resistance crisis. The emergence of multiantibiotic-resistant bacteria, often referred to as superbugs, is leading to infections that are increasingly difficult to treat. Further, bacteria have evolved mechanisms by which they subvert the immune response, meaning that even antibiotic-sensitive bacteria can persist through antibiotic therapy. For these reasons, a broad range of viable therapeutic alternatives or conjunctions to traditional antimicrobial therapy are urgently required to reduce the burden of disease threatened by antibiotic resistance. Immunotherapy has emerged as a leading treatment option in cancer, and researchers are now attempting to apply this to infectious disease. This review summarizes and discusses the recent advances in the field and highlights current and future perspectives of using immunotherapies to treat bacterial infections. The emergence of multiantibiotic-resistant bacteria, often referred to as superbugs, is leading to infections that are increasingly difficult to treat. Further, bacteria have evolved mechanisms by which they subvert the immune response, meaning that even antibiotic-sensitive bacteria can persist through antibiotic therapy. For these reasons, a broad range of viable therapeutic alternatives or conjunctions to traditional antimicrobial therapy are urgently required to reduce the burden of disease threatened by antibiotic resistance. Immunotherapy has emerged as a leading treatment option in cancer, and researchers are now attempting to apply this to infectious disease. This review summarizes and discusses the recent advances in the field and highlights current and future perspectives of using immunotherapies to treat bacterial infections. an aggregate of immune cells, predominantly macrophages, which act to constrain infectious organisms in order to prevent dissemination. A granuloma can also contribute to the persistence of infection by hiding infectious organisms from the immune response or from antimicrobial drugs. liver-resident macrophages. macrophages have been historically classified into two polarization states, with proinflammatory macrophages designated ‘M1’ or ‘classically activated’, and anti-inflammatory macrophages designated ‘M2’ or ‘alternatively activated’. While it is now clear that this paradigm is outdated and does not reflect the true spectrum of macrophage classifications, we have used ‘M1-like’ and ‘M2-like’ here for simplicity in describing macrophages with bactericidal or regulatory phenotypes, respectively. subpopulations of bacteria which have transient tolerance to antibiotic therapy due to dormancy induced in response to environmental stress. This tolerant state differs from that of antibiotic-resistant bacteria, which arises from heritable mutations, as the progeny of persister cells revert to antibiotic sensitivity when replicating. Persister cells are thought to be a major contributor to recalcitrance and relapse of certain persistent bacterial infections. a subpopulation of bacteria with attenuated growth as a result of mutations, usually in genes encoding the electron transport chain or thymidine biosynthesis, allowing them to tolerate antibiotic therapy while also surviving within host cells. Similar to persister cells, this contributes to persistence of infection; however, in the case of small-colony variants persistence is due to heritable and permanent changes in bacterial growth as opposed to transient adaptations to environmental stress.
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